IDSI Faculty Advisory Board Dr. Carter Butts Research Paper “Mutation Effects on Structure and Dynamics: Adaptive Evolution of the SARS-CoV-2 Main Protease”

In addition to basic structural properties such as variation in surface area and torsion angles, we use protein structure networks and active site networks to evaluate functionally relevant characters related to global cohesion and active site constraint. Substitution analysis shows a continuing trend toward more hydrophobic residues that are dependent on the location of the residue in primary, secondary, tertiary, and quaternary structures. Phylogenetic analysis provides additional evidence for the impact of selective pressure on mutation of M^pro. Overall, these analyses suggest evolutionary adaptation of M^pro toward more hydrophobicity and a less-constrained active site in response to the selective pressures of a novel host environment.